About Potocki-Lupski (dup17p11.2) Syndrome
Individuals with the genetic condition designated as dup(17)(p11.2p11.2) (OMIM #610883), or dup 17p carry extra genetic information (known as a duplication) on the short arm of chromosome 17.
Each cell of the body should have 23 pairs of chromosomes (22 numbered chromosomes and one pair of sex chromosomes; XX for females and XY for males) that contain the complete genetic information (genome) for the individual. When the egg and sperm cells are formed, the pairs of chromosomes are separated in a process called meiosis, so that each egg or sperm contains only one copy of each chromosome. Errors that occur during this process can result in genomic imbalances such as missing or extra genetic material. These imbalances can cause genetic syndromes that are associated with a wide variety of clinical outcomes.
Many genetic syndromes that were first described on the basis of clinical findings were later found to be caused by genomic imbalances. New high-resolution laboratory tests—known as chromosomal microarray analysis or CMA can now detect these genomic imbalances even when a particular syndrome is not suspected.
Two distinct conditions result from errors in meiotic recombination involving the short arm of chromosome 17:
Smith-Magenis syndrome (SMS – OMIM #182290) is caused by a deletion, or loss of genetic material, on one copy of chromosome 17. This well-known syndrome is associated with developmental delay, mental retardation, congenital anomalies such as heart and kidney defects, and neurobehavioral abnormalities such as severe sleep disturbances and self-injurious behavior.
For every chromosomal deletion, there exists a reciprocal chromosomal duplication. Although the genomic mechanism for the deletion and duplication is the same, the clinical features of individuals are different. These duplication syndromes have their own distinct clinical features and should not be confused with the deletion syndromes.
Potocki-Lupski Syndrome (PTLS)
Duplication of chromosome 17p11.2 – Potocki-Lupski syndrome (PTLS) (OMIM #610883) is a newly recognized genetic condition with only a few dozen cases reported in the medical literature. Patients who have this duplication often have low muscle tone, poor feeding, and failure to thrive during infancy, and also present with delayed development of motor and verbal milestones. Many individuals who have PTLS have difficulty with articulation and language processing. In addition, patients may have behavioral characteristics similar to those seen in persons with autism or autism-spectrum disorders. Individuals with PTLS may have heart defects and sleep apnea. The facial features observed in PTLS are subtly similar between individuals but are not usually described as abnormal or striking by physicians.
While fewer than 50 persons with duplication 17p11.2 have been described in the medical literature, we know that this duplication is predicted to be observed in at least 1 in 20,000 individuals. Although PTLS is considered a “chromosomal” disorder, diagnosis is often missed on a routine chromosome analysis. Due to technological advances in cytogenetics, specifically the use of array comparative genomic hybridization (aCGH) for genetic diagnosis, microdeletions and microduplications can be detected with equal fidelity. Hundreds of chromosome segments can be analyzed at one time searching for chromosomal imbalances. We anticipate that many more individuals will be diagnosed with dup 17p11.2 as this testing is performed more routinely in persons with developmental delay, mental retardation, and/or autism spectrum disorder.
While most people with PTLS have a duplication only within the 17p11.2 region, some PTLS patients have a larger duplication that extends to the Charcot-Marie-Tooth (CMT) region of 17p12 and includes the PMP22 gene. The array comparative genomic hybridization test can detect whether or not a person is duplicated for PMP22. An individual with a larger duplication that includes PMP22 will also have CMT type 1A which affects the peripheral nervous system, and is the most common type of CMT. The CMT Association is an excellent resource.
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